{"entity": "publication", "iuid": "70d8595b7f524892aced629b61e2eba4", "timestamp": "2026-08-22T08:30:45.301Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/70d8595b7f524892aced629b61e2eba4.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/70d8595b7f524892aced629b61e2eba4"}}, "title": "Evaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model.", "authors": [{"family": "Leitao", "given": "Charles Dahlsson", "initials": "CD"}, {"family": "Rinne", "given": "Sara S", "initials": "SS"}, {"family": "Altai", "given": "Mohamed", "initials": "M"}, {"family": "Vorontsova", "given": "Olga", "initials": "O"}, {"family": "Dun\u00e5s", "given": "Finn", "initials": "F"}, {"family": "Jonasson", "given": "Per", "initials": "P"}, {"family": "Tolmachev", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-6122-1734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/896ae9fae8b74251afe11b4354c62794.json"}}, {"family": "L\u00f6fblom", "given": "John", "initials": "J", "orcid": "0000-0001-9423-0541", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bf8479d43c1c45efb85ba0c0da634aeb.json"}}, {"family": "St\u00e5hl", "given": "Stefan", "initials": "S"}, {"family": "Orlova", "given": "Anna", "initials": "A", "orcid": "0000-0001-6120-2683", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1c374f429702489494c05f84f298b4b7.json"}}], "type": "journal article", "published": "2020-06-13", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "12", "issue": "6", "issn-l": null}, "abstract": "Human epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis. We have previously evaluated the biodistribution profiles of five mono- and bivalent anti-HER3 affibody molecules (designated as 3) fused to an albumin-binding domain (designated as A), 3A, 33A, 3A3, A33, and A3, that inhibit ligand-dependent phosphorylation. In the present study, we examined the therapeutic efficacy of the three most promising variants, 3A, 33A, and 3A3, in a direct comparison with the HER3-targeting monoclonal antibody seribantumab (MM-121) in a preclinical BxPC-3 pancreatic cancer model. Xenografted mice were treated with either an affibody construct or MM-121 and the tumor growth was compared to a vehicle group. Receptor occupancy was estimated by positron emission tomography/computed tomography (PET/CT) imaging using a HER3-targeting affibody imaging agent [68Ga]Ga-(HE)3-Z08698-NODAGA. The affibody molecules could inhibit ligand-dependent phosphorylation and cell proliferation in vitro and demonstrated tumor growth inhibition in vivo comparable to that of MM-121. PET/CT imaging showed full receptor occupancy for all tested drug candidates. Treatment with 3A and 3A3 affibody constructs was more efficient than with 33A and similar to the anti-HER3 antibody seribantumab, showing that the molecular design of affibody-based therapeutics targeting HER3 in terms of the relative position of functional domains and valency has an impact on therapeutic effect.", "doi": "10.3390/pharmaceutics12060551", "pmid": "32545760", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7356278"}, {"db": "pii", "key": "pharmaceutics12060551"}], "notes": [], "created": "2026-08-21T13:04:42.755Z", "modified": "2026-08-21T13:04:42.820Z"}